Novel MHC Class I Structures on Exosomes
Novel MHC Class I Structures on Exosomes
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DOI：
10.4049/jimmunol.0900798
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发表时间：
2009-08-01
影响因子：
4.4
通讯作者：
Powis, Simon J.
中科院分区：
文献类型：
--
作者：
Lynch, Sarah;Santos, Susana G.;Powis, Simon J.
外泌体是由包括免疫系统在内的许多细胞类型释放的纳米大小的囊泡，通常含有许多免疫识别分子，包括MHC分子。我们在这项研究中证明，外泌体可以以二硫化物连接的MHC I二聚体的形式显示其MHC I类（MHC I）含量的显著比例。这些MHC I二聚体可以从各种细胞系、人单核细胞来源的树突状细胞释放后检测到，也可以在人血浆中发现。外泌体相关二聚体表现出新的特征，包括1)由折叠的MHC I组成，通过构象依赖性抗体检测，2)在两个不同的MHC I等位基因之间形成二聚体。我们发现二聚体的形成是通过位于许多MHC I分子的细胞质尾部区域的半胱氨酸残基介导的，并且与全细胞裂解物相比，外泌体中的谷胱甘肽水平较低。我们提出这些外泌体MHC I二聚体作为免疫受体识别的新结构。免疫学杂志，2009,(3):1884-1891。
Exosomes are nanometer-sized vesicles released by a number of cell types including those of the immune system, and often contain numerous immune recognition molecules including MHC molecules. We demonstrate in this study that exosomes can display a significant proportion of their MHC class I (MHC I) content in the form of disulfide-linked MHC I dimers. These MHC I dimers can be detected after release from various cell lines, human monocyte-derived dendritic cells, and can also be found in human plasma. Exosome-associated dimers exhibit novel characteristics which include 1) being composed of folded MHC I, as detected by conformational-dependent Abs, and 2) dimers forming between two different MHC I alleles. We show that dimer formation is mediated through cysteine residues located in the cytoplasmic tail domains of many MHC I molecules, and is associated with a low level of glutathione in exosomes when compared with whole cell lysates. We propose these exosomal MHC I dimers as novel structures for recognition by immune receptors. The Journal of Immunology, 2009, 183: 1884-1891.